Ototoxicity of cis-diamminedichloroplatinum (II): influence of dose, schedule and mode of administration

Abstract

During and after 233 cycles of cis-diamminedichloroplatinum (II) (CDDP), 197 serial audiograms were obtained in 48 patients and compared with baseline audiograms. Use was made of three dose schedules (20 mg/m2, 25-50 mg/m2 and 70-120 mg/m2), two regimens (single-day or daily for 5 days) and three modes of administration (rapid infusion, 2- or 3-hr infusion, 24-hr infusion). Clinical hearing loss occurred in 12.5% and tinnitus in 25% of all patients. The incidence of audiographic changes (65% overall, 81% bilaterally) increased with increasing cumulative CDDP dose independent of treatment schedule. The incidence was correlated with the daily dose (P = 0.0037) and changes were more severe after single high doses. No difference was found between the single low dose and the daily for 5 days regimen. Rapid infusion of a single high dose was more ototoxic than a 24-hr infusion of the same dose (P = 0.0015). It is concluded that, compared with the single high-dose regimen, the daily low dose for 5 days is preferable in cases where the patient might be cured by a regimen including CDDP.